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Synthetic Genetic Targeting of Genome Instability in Cancer
Manitoba Institute of Cell Biology, Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba R3E 0V9, Canada
* Author to whom correspondence should be addressed.
Received: 23 April 2013; in revised form: 3 June 2013 / Accepted: 6 June 2013 / Published: 24 June 2013
Abstract: Cancer is a leading cause of death throughout the World. A limitation of many current chemotherapeutic approaches is that their cytotoxic effects are not restricted to cancer cells, and adverse side effects can occur within normal tissues. Consequently, novel strategies are urgently needed to better target cancer cells. As we approach the era of personalized medicine, targeting the specific molecular defect(s) within a given patient’s tumor will become a more effective treatment strategy than traditional approaches that often target a given cancer type or sub-type. Synthetic genetic interactions are now being examined for their therapeutic potential and are designed to target the specific genetic and epigenetic phenomena associated with tumor formation, and thus are predicted to be highly selective. In general, two complementary approaches have been employed, including synthetic lethality and synthetic dosage lethality, to target aberrant expression and/or function associated with tumor suppressor genes and oncogenes, respectively. Here we discuss the concepts of synthetic lethality and synthetic dosage lethality, and explain three general experimental approaches designed to identify novel genetic interactors. We present examples and discuss the merits and caveats of each approach. Finally, we provide insight into the subsequent pre-clinical work required to validate novel candidate drug targets.
Keywords: cancer; genome instability; tumor suppressor gene; oncogene; synthetic genetic approach; synthetic lethality; synthetic dosage lethality; cancer therapy
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MDPI and ACS Style
Sajesh, B.V.; Guppy, B.J.; McManus, K.J. Synthetic Genetic Targeting of Genome Instability in Cancer. Cancers 2013, 5, 739-761.
Sajesh BV, Guppy BJ, McManus KJ. Synthetic Genetic Targeting of Genome Instability in Cancer. Cancers. 2013; 5(3):739-761.
Sajesh, Babu V.; Guppy, Brent J.; McManus, Kirk J. 2013. "Synthetic Genetic Targeting of Genome Instability in Cancer." Cancers 5, no. 3: 739-761.